SALL4 Protein Reexpressed in Subset of Patients With HCC
SALL4-positive hepatocellular carcinoma exhibits overexpression of proliferative, metastatic genes
WEDNESDAY, June 12 (HealthDay News) -- The oncofetal protein SALL4 is expressed in a subgroup of patients with hepatocellular carcinoma, with overexpression of proliferative and metastatic genes observed in SALL4-positive hepatocellular carcinomas, according to a study published in the June 13 issue of the New England Journal of Medicine.
Kol Jia Yong, from the Cancer Science Institute of Singapore, and colleagues screened specimens from patients with primary hepatocellular carcinoma for SALL4 expression and conducted a clinicopathological analysis. The role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy was assessed.
The researchers found that the oncofetal protein SALL4 was silenced in the adult liver, but was reexpressed in a subgroup of patients with hepatocellular carcinoma and an unfavorable prognosis. In SALL4-positive hepatocellular carcinomas, enrichment of progenitor-like gene signatures was observed, with overexpression of proliferative and metastatic genes noted in gene-expression analysis. The critical role of SALL4 in cell survival and tumorigenicity was confirmed in loss-of-function studies. In in-vivo xenograft models, blocking SALL4-corepressor interactions released the phosphatase and tensin homologue protein suppression and inhibited tumor formation.
"SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype," the authors write. "The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma."
Full Text (subscription or payment may be required) (http://www.nejm.org/doi/full/10.1056/NEJMoa1300297?query=featured_home )Editorial (subscription or payment may be required) (http://www.nejm.org/doi/full/10.1056/NEJMe1303026?query=featured_home )